LONG TERM BIODEGRADATION OF ELASTOMERIC BIOMATERIALS

拟议的研究计划是对现有研究的延伸 旨在对生物相容性和 生物医用弹性体，特别是聚氨酯的生物稳定性。这个 总体目标是测试提出的假设 植入型聚醚氨酯(PEUS)的生物降解 细胞/聚合物反馈机制。蛋白质的初始吸附 影响随后的细胞黏附和激活。后者可以 紧随其后的是呼吸爆发，产生的氧气物种 最有可能导致聚合物链的氧化降解。 改变的表面属性和降解产物可以进一步 影响蛋白质吸附和/或细胞黏附的过程 通过反馈机制激活。同时，细胞的胞吐作用 溶酶体酶和其他介质可能会导致其他细胞成为 激活了。 为了确认和/或修改该假设并 建立运行机制，开展实验程序 含和不含特定添加剂的已知成分的PEUS 增强生物稳定性。实验程序建议如下：1) 测定人血浆蛋白在候选PEUS上的吸附 使用放射免疫分析(RIA)或免疫金蛋白A标记 扫描电子显微镜(SEM)；2)定量测量细胞 使用CAGE种植体系统进行粘连和激活；3)表征 用光学显微镜(OM)和扫描电子显微镜观察植入PEU的表面腐蚀 通过ATR-FTIR和GPC分析确定提取物的化学变化， 并确定对包括疲劳在内的性能特性的影响 抗性；4)评估单核细胞呼吸爆发介导的peu降解 单核/巨噬细胞体外培养体系；5)建立 金属离子体外氧化降解苯丙氨酸的化学 催化过氧化氢处理和加速条件。

The proposed research program is an extension of current studies directed toward a fundamental understanding of biocompatibility and biostability of biomedical elastomers, specifically polyurethanes. The overall objective is to test the proposed hypothesis for the biodegradation of implanted poly(etherurethanes) (PEUs) which involves cell/polymer feedback mechanism. The Initial adsorption of proteins affects the subsequent cellular adhesion and activation. The latter may be followed by a respiratory burst which produces oxygen species that are most likely responsible for oxidative degradation of the polymer chain. The altered surface properties and degradation products may further affect the process of protein adsorption and/or cell adhesion and activation via feedback mechanisms. Simultaneously, the exocytosis of lysosomal enzymes and other mediators may cause other cells to become activated. In order to confirm and/or modify the hypothesis and to establish operative mechanisms, experimental procedures will be carried out on PEUs of known composition, with and without specific additives to enhance biostability. Experimental procedures are proposed to: 1) Determine the adsorption of human blood plasma proteins to candidate PEUs using radioimmunoassay (RIA) or immunogold protein A labelling with scanning electron microscopy (SEM); 2) Quantitatively measure cell adhesion and activation using the cage implant system; 3) Characterize surface 'corrosion' of implanted PEUs using optical microscopy (OM) and SEM, identify chemical changes by ATR-FTIR and GPC analysis of extracts, and determine the effects on performance properties including fatigue resistance; 4) Assess monocyte respiratory burst mediated PEU degradation in vitro with the monocyte/macrophage culture system; and 5) Establish the chemistry of oxidative degradation of PEUs in vitro using metal- catalyzed peroxide treatment and accelerated conditions.